Nao Kakizawa

Risk factors for intra-abdominal infection after pancreaticoduodenectomy - a retrospective analysis to evaluate the significance of preoperative biliary drainage and postoperative pancreatic fistula.

BACKGROUND/AIMS Intra-abdominal infection (IAI) after pancreaticoduodenectomy (PD) is a common cause of prolongation of postoperative hospital stay and readmission to the hospital following discharge. METHODOLOGY Two hundred and six patients undergoing PD were reviewed to investigate the risk factors for IAI after PD. Patients were separated into two groups: those who developed IAI after PD (Group A; n=44), and those who had not developed IAI after PD (Group B; n=162), the two groups were then compared to identify the risk factors for IAI after PD. A hundred and six patients (51.5%) underwent preoperative biliary drainage (PBD). RESULTS Multivariate analysis revealed that pancreatic fistula (PF) was an independent risk factor for IAI after PD (p<0.001; odds ratio=9.58; 95% confidence interval=4.37-21.0), but PBD was not a significant risk factor. CONCLUSIONS We demonstrated that the adequate PBD might not affect IAI after PD. On the other hand, PF was an independent risk factor for IAI after PD. A large randomized controlled trial, which would prove the effect of early removal of a prophylactic placed drain to prevent IAI, should be planned.

En bloc pancreaticoduodenectomy and right hemicolectomy for locally advanced right-sided colon cancer

AIM To assess the usefulness of en bloc right hemicolectomy with pancreaticoduodenectomy (RHCPD) for locally advanced right-sided colon cancer (LARCC). METHODS We retrospectively reviewed the database of Saitama Medical Center, Jichi Medical University, between January 2009 and December 2016. During this time, 299 patients underwent radical right hemicolectomy for right-sided colon cancer. Among them, 5 underwent RHCPD for LARCC with tumor infiltration to adjacent organs. Preoperative computed tomography (CT) was routinely performed to evaluate local tumor infiltration into adjacent organs. During the operation, we evaluated the resectability and the amount of infiltration into the adjacent organs without dissecting the adherent organs from the cancer. When we confirmed that radical resection was feasible and could lead to R0 resection, we performed RHCPD. The clinical data were carefully reviewed, and the demographic variables, intraoperative data, and postoperative parameters were recorded. RESULTS The median age of the 5 patients who underwent RHCPD for LARCC was 70 years. The tumors were located in the ascending colon (three patients) and transverse colon (two patients). Preoperative CT revealed infiltration of the tumor into the duodenum in all patients, the pancreas in four patients, the superior mesenteric vein (SMV) in two patients, and tumor thrombosis in the SMV in one patient. We performed RHCPD plus SMV resection in three patients. Major postoperative complications occurred in 3 patients (60%) as pancreatic fistula (grade B and grade C, according to International Study Group on Pancreatic Fistula Definition) and delayed gastric empty. None of the patients died during their hospital stay. A histological examination confirmed malignant infiltration into the duodenum and/or pancreas in 4 patients (80%), and no patients showed any malignant infiltration into the SMV. Two patients were histologically confirmed to have tumor thrombosis in the SMV. All of the tumors had clear resection margins (R0). The median follow-up time was 77 mo. During this period, two patients with tumor thrombosis died from liver metastasis. The overall survival rates were 80% at 1 year and 60% at 5 years. All patients with node-negative status (n = 2) survived for more than seven years. CONCLUSION This study showed that the long-term survival is possible for patients with LARCC if RHCPD is performed successfully, particularly in those with node-negative status.

Clinical and molecular assessment of regorafenib monotherapy.

Regorafenib has shown survival benefits in metastatic colorectal cancer patients who were exacerbated after all standard therapies. Some patients, however, exhibit severe adverse events (AEs) resulting in treatment discontinuation. Therefore, the selection of patients likely to benefit from regorafenib is crucial. Twenty patients were treated with regorafenib for metastatic colorectal cancer; 122 plasma samples were taken from 16 of these patients for monitoring of circulating tumor DNA (ctDNA) in the blood. The treatment response, AEs, overall survival (OS), progression-free survival (PFS) and tumor morphologic changes on CT images were evaluated. KRAS mutant ctDNA was determined using digital PCR. Median PFS and OS were 2.5 and 5.9 months, respectively. Treatment was discontinued because of disease progression (PD) in 10 patients, and AEs in another 10 patients. AEs included hyperbilirubinemia, severe fatigue and skin rash. Hyperbilirubinemia was seen in two patients with multiple bilateral liver metastases, and severe fatigue in another 2 patients with poor performance status (PS). These severe AEs resulted in treatment discontinuation. Ten patients had a median PFS of 2.1 months with AE related discontinuation; PD occurred at 3.5 months (p=0.00334). Four patients exhibited a morphologic response, achieving better PFS times of 3.5, 5.3, 5.6 and 14.2 months. Emergence of the KRAS mutation in ctDNA was observed during anti-EGFR antibody treatment in 3 patients among 11 with KRAS wild-type tumors; it was detectable in the blood prior to radiographic detection of PD. Moreover, the KRAS mutation declined in two patients during regorafenib monotherapy. These patients were re-challenged with anti-EGFR antibody. Patients with extensive multiple liver metastases or poor PS are unlikely to benefit from regorafenib. Patients with a morphologic response will probably benefit from regorafenib with adequate management of other AEs. KRAS monitoring in ctDNA could be useful regarding treatment response and in determining treatment strategy.

Laparoscopic resection of retroperitoneal ectopic thyroid tissue: Retroperitoneal ectopic thyroid tissue

A 43‐year‐old otherwise healthy woman was found to have a retroperitoneal mass during a routine medical examination and was referred for further evaluation. Abdominal CT scan showed a well‐delineated, low‐density area that exhibited heterogeneous contrast enhancement. The area measured about 20 mm in size and was to the left of the aorta at the level of the inferior mesenteric artery. MRI showed a mass with heterogeneous hypointensity on T1‐weighted images and heterogeneous hyperintensity on T2‐weighted images. PET‐CT scan showed slightly increased 18F‐fluorodeoxyglucose accumulation within the mass. Laparoscopic resection was performed. A smooth, brownish mass was seen in the retroperitoneum and was resected with minimal blood loss. Histopathological examination showed a nodular mass measuring 40 × 26 × 20 mm that was composed solely of ectopic thyroid tissue. This case shows the exceptional development of ectopic thyroid in the infradiaphragmatic retroperitoneum and demonstrates the usefulness of laparoscopy for resecting such masses.

Monitoring circulating tumor DNA revealed dynamic changes in KRAS status in patients with metastatic colorectal cancer

KRAS mutated circulating tumor DNA (MctDNA) can be monitored in the blood of patients with metastatic colorectal cancer (mCRC), but dynamic changes have not been determined. Four hundred and fifty-seven plasma samples were collected prospectively from 85 mCRC patients who underwent chemotherapy. MctDNA in plasma was detected by droplet digital PCR, and the percentage of MctDNA in total circulating cell-free DNA was calculated. KRAS assessment in tumor tissues showed 29 patients with the mutant-type (MT) and 56 patients with the wild-type (WT). Twenty-three of 29 MT patients (79.3%) and 28 of 56 WT patients (50.0%) showed MctDNA. Emergence of MctDNA was recognized during treatments with various drugs. Regardless of KRAS status in tumor tissues, patients with MctDNA in blood showed poor progression-free survival with first-line treatment. Median percentage of MctDNA accounted for 10.10% in MT patients and 0.22% in WT patients. These differences between MT and WT likely affected patterns of changes in MctDNA. KRAS monitoring identified dynamic changes in MctDNA, such as continuous, intermittent, and transient changes (quick elevation and disappearance). Emergence of MctDNA involved drug resistance, except for transient changes, which were seen in WT patients and likely corresponded with the drug response. Transient changes could be involved in recovery of sensitivity to anti-EGFR antibody in WT patients. Monitoring MctDNA during various treatments showed dynamic changes in KRAS status and could provide useful information for determining treatments for patients with mCRC.

Morphological response contributes to patient selection for rescue liver resection in chemotherapy patients with initially un-resectable colorectal liver metastasis

Morphological response is considered an improved surrogate to the Response Evaluation Criteria in Solid Tumors (RECIST) model with regard to predicting the prognosis for patients with colorectal liver metastases. However, its use as a decision-making tool for surgical intervention has not been examined. The present study assessed the morphological response in 50 patients who underwent chemotherapy with or without bevacizumab for initially un-resectable colorectal liver metastases. Changes in tumor morphology between heterogeneous with uncertain borders and homogeneous with clear borders were defined as an optimal response (OR). Patients were also assessed as having an incomplete response (IR), and an absence of marked changes was assessed as no response (NR). No significant difference was observed in progression-free survival (PFS) between complete response/partial response (CR/PR) and stable disease/progressive disease (SD/PD), according to RECIST. By contrast, PFS for OR/IR patients was significantly improved compared with that for NR patients (13.2 vs. 8.7 months; P=0.0426). Exclusion of PD enhanced the difference in PFS between OR/IR and NR patients (15.1 vs. 9.3 months; P<0.0001), whereas no difference was observed between CR/PR and SD. The rate of OR and IR in patients treated with bevacizumab was 47.4% (9/19), but only 19.4% (6/31) for patients that were not administered bevacizumab. Comparison of the survival curves between OR/IR and NR patients revealed similar survival rates at 6 months after chemotherapy, but the groups exhibited different survival rates subsequent to this period of time. Patients showing OR/IR within 6 months appeared to be oncologically stable and could be considered as candidates for surgical intervention, including rescue liver resection. Comparing the pathological and morphological features of the tumor with representative optimal response, living tumor cells were revealed to be distributed within the area of vascular reconstruction induced by bevacizumab, resulting in a predictive value for prognosis in the patients treated with bevacizumab. The present findings provided the evidence for physicians to consider patients with previously un-resectable metastatic colorectal cancer as candidates for surgical treatment. Morphological response is a useful decision-making tool for evaluating these patients for rescue liver resection following chemotherapy.

Heterogeneous expression of zinc-finger E-box-binding homeobox 1 plays a pivotal role in metastasis via regulation of miR-200c in epithelial-mesenchymal transition.

Although epithelial-mesenchymal transition (EMT) has been implicated as the pivotal event in metastasis, there is insufficient evidence related to EMT in clinical settings. Intratumor heterogeneity may lead to underestimation of gene expression representing EMT. In the present study, we investigated the expression of EMT-associated genes and microRNAs in primary colorectal cancer while considering intratumor heterogeneity. One-hundred and thirty-three multiple spatially separated samples were obtained from 8 patients with metastatic colorectal cancers and 8 with non-metastatic colorectal cancers, from the tumor center (TC), invasive front (IF) and metastasis. Differences in gene and microRNA expression were investigated by microarray and quantitative reverse-transcription PCR. Gene expression microarray analysis detected 7920 sites showing differing levels of gene expression among the TC, IF and metastasis. Expression of the EMT-associated gene zinc-finger E-box-binding homeobox 1 (ZEB1) significantly increased in the IF (p<0.01). To exclude individual differences, the expression ratio between TC and IF in each tumor was applied to analysis. This approach enabled recognition of the activation of the VEGF and Wnt signaling pathways, which were involved in metastasis via promotion of EMT. While no activation of these pathways was seen at the TC, regardless of whether tumors were metastatic or non-metastatic, they were preferentially activated at the IF in metastatic tumors, where high ZEB1 expression was seen in connection with decreased miR-200c expression. Multiple sampling in a tumor revealed that heterogeneous ZEB1 expression induced by EMT-associated signaling pathways played a pivotal role in metastasis via regulation of miR-200c.

The surgical treatment of acute and severe diversion colitis mimicking ulcerative colitis: a case report

BackgroundDiversion colitis (DC) is characterized by nonspecific inflammation in the remaining colon or rectum, and loss of the fecal stream plays a major role in the disease’s development. Although the majority of patients are asymptomatic, medical and/or surgical treatment is required for those who are symptomatic. There is a particular interest on how to manage patients with acute and severe clinical presentations, but the pathogenesis is not fully understood. We report the rare case of a man with acute and severe DC mimicking ulcerative colitis (UC) with extra-intestinal manifestations that was successfully managed with surgical treatment.Case presentationA 68-year-old man with a history of laparoscopic intersphincteric resection of the rectum with diverting loop ileostomy for lower rectal cancer suffered from anastomotic stenosis requiring repeated endoscopic dilatation. His loop stoma was not reversed because these treatments were unsuccessful. He denied having a history of inflammatory bowel disease. Twelve years postoperatively, he developed a perineal abscess requiring drainage. Subsequently, he developed a high-grade fever, bloody discharge per anus, and skin ulcers in the right ankle and around the stoma. Because culture tests were negative for bacteria, it was deemed that his acute illness reflected an inflammatory response rather than an infectious disease. Colonoscopy revealed anastomotic stenosis, a colonic fistula, and mucosa that hemorrhaged easily, with lacerations. A pathological examination with biopsy revealed inflammatory infiltration without malignancy. After reviewing the patient’s clinical episodes and discussing the case with physicians in multiple specialties, we performed total colectomy with end ileostomy in accordance with the abdominoperineal resection. The postoperative course was uneventful. A resected specimen showed atrophic mucosa with the disappearance of haustra in the distal colon, as well as edematous and dilated mucosa in the proximal colon. The pathological diagnosis was suggestive of UC, including erosion and ulceration in edematous wall, crypt abscess, and inflammatory infiltration into the mucosa. The skin ulcers in the right ankle and around the stoma healed over time.ConclusionsDC can eventuate in a long-term period after fecal diversion surgery, possibly with extra-intestinal manifestations mimicking UC. Surgical treatment seems feasible for patients with acute and severe DC.

Intussusception secondary to descending colon lipoma presenting with simultaneous acute appendicitis

Abstract We report a patient with a descending colon lipoma presenting with hematochezia who developed intussusception, which was simultaneously accompanied by acute appendicitis. A 43-year-old man presented with hematochezia. Colonoscopy revealed a submucosal tumor with a reddish surface in the descending colon. A solid mass with fat density value measuring 5 cm in diameter was observed in the descending colon on CT. While awaiting elective resection, the patient developed lower abdominal pain. CT demonstrated antegrade colo-colonic intussusception in the descending colon. Simultaneously, the appendix was inflamed with a high density intraluminal lesion suspected to be a fecalith. The diagnosis of simultaneous intussusception and acute appendicitis was made. Appendectomy and partial resection of the descending colon was performed. Histopathological examination was consistent with descending colon lipoma and acute appendicitis. The mechanism for developing hematochezia and the risk for development of colo-colonic intussusception due to large colon lipoma and acute appendicitis were highlighted.

Laparoscopic and percutaneous repair of a large midline incisional hernia extending to the bilateral subcostal region: A case report

Highlights • A hybrid laparoscopic and percutaneous repair for incisional hernia was described.• Percutaneous defect closure can be indicated for large hernia (>10 cm in diameter).• Mesh fixation should be limited below the costal margin in subcostal hernia.• Minimal organ injuries and obtaining more overlap are the advantages.• Postoperative pain is the disadvantage.